ArticleMammalian genome : official journal of the International Mammalian Genome Society2013
Creation and characterization of BAC-transgenic mice with physiological overexpression of epitope-tagged RCAN1 (DSCR1).
Article in Mammalian genome : official journal of the International Mammalian Genome Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci.Human molecular genetics · 2016Trial
- RCAN1-mediated calcineurin inhibition as a target for cancer therapy.Molecular medicine (Cambridge, Mass.) · 2022Review
- Enhanced Production of Herpes Simplex Virus 1 Amplicon Vectors by Gene Modification and Optimization of Packaging Cell Growth Medium.Molecular therapy. Methods & clinical development · 2020Article
- Mediation of the Acute Stress Response by the Skeleton.Cell metabolism · 2019Article
- RCAN1 Knockdown Reverts Defects in the Number of Calcium-Induced Exocytotic Events in a Cellular Model of Down Syndrome.Frontiers in cellular neuroscience · 2018Article
- Rodent models in Down syndrome research: impact and future opportunities.Disease models & mechanisms · 2017Review
- Trans-acting epigenetic effects of chromosomal aneuploidies: lessons from Down syndrome and mouse models.Epigenomics · 2017Review
- Mouse-based genetic modeling and analysis of Down syndrome.British medical bulletin · 2016Review
- RCAN1 overexpression promotes age-dependent mitochondrial dysregulation related to neurodegeneration in Alzheimer's disease.Acta neuropathologica · 2015Article
- Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models.Genome biology · 2015Article
- Article
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10 authors at 3 institutions in 1 country.
Funding
Abstract
The chromosome 21 gene RCAN1, encoding a modulator of the calcineurin (CaN) phosphatase, is a candidate gene for contributing to cognitive disability in people with Down syndrome (DS; trisomy 21). To develop a physiologically relevant model for studying the biochemistry of RCAN1 and its contribution to DS, we generated bacterial artificial chromosome-transgenic (BAC-Tg) mouse lines containing the human RCAN1 gene with a C-terminal HA-FLAG epitope tag incorporated by recombineering. The BAC-Tg was expressed at levels only moderately higher than the native Rcan1 gene: approximately 1.5-fold in RCAN1 (BAC-Tg1) and twofold in RCAN1 (BAC-Tg2). Affinity purification of the RCAN1 protein complex from brains of these mice revealed a core complex of RCAN1 with CaN, glycogen synthase kinase 3-beta (Gsk3b), and calmodulin, with substoichiometric components, including LOC73419. The BAC-Tg mice are fully viable, but long-term synaptic potentiation is impaired in proportion to BAC-Tg dosage in hippocampal brain slices from these mice. RCAN1 can act as a tumor suppressor in some systems, but we found that the RCAN1 BAC-Tg did not reduce mammary cancer growth when present at a low copy number in Tp53;WAP-Cre mice. This work establishes a useful mouse model for investigating the biochemistry and dose-dependent functions of the RCAN1 protein in vivo.
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Registered trials
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